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Scatter plot analyses for 14,169 phenylethanes of the substructure C

A novel N,N-dibenzyl diaminomethylenemalononitrile organocatalyst efficiently promoted asymmetric Henry reactions of trifluoromethyl enones with nitromethane, affording corresponding highly functionalized products in high yields with excellent enantioselectivities (up to 90% ee). This study is the first to report the successful example of the asymmetric 1,2-additions of nitromethane to trifluoromethyl enones.

A calix-shaped polyoxometalate, [V12O32]4&minus, (V12), stabilizes an anion moiety in its central cavity. This molecule-sized container has the potential to control the reactivity of an anion. The highly-reactive cyanate is smoothly trapped by V12 to form [V12O32(CN)]5&minus, In the CH3NO2 solution, cyanate abstracts protons from CH3NO2, and the resultant CH2NO2&minus, is stabilized in V12 to form [V12O32(CH2NO2)]5&minus, (V12(CH2NO2)). A crystallographic analysis revealed the double-bond characteristic short bond distance of 1.248 &Aring, between the carbon and nitrogen atoms in the nitromethane anion in V12. 1H and 13C NMR studies showed that the nitromethane anion in V12 must not be exchanged with the nitromethane solvent. Thus, the V12 container restrains the reactivity of anionic species.

A continuous-flow synthesis of β-nitroolefins by using heterogeneous base catalysts has been developed. Although the use of an excess amount of nitro-donor such as nitromethane is required in conventional methods, nearly equimolar amounts of nitro-donors and carbonyl compounds are sufficient for high-yielding production of nitroolefins. Catalysts for this flow protocol are inexpensive and abundant, and high durability and high productivity were also realized by using an appropriate second support.

Breast and prostate cancers are frequently treated with chemotherapy. Several novel chemicals are being reported for this purpose, particularly synthetic and natural benzophenones. This work reports the synthesis of substituted 2-hydroxybenzophenones through 1,4-conjugate addition/intramolecular cycloaddition/dehydration of nitromethane on key intermediate chromones. Structures were extensively studied by means of 2D NMR spectroscopy and single-crystal XRD. Their cytotoxicity was evaluated in vitro in two breast cancer cell lines (MDA-MB-231 and T47-D) and one prostate cancer cell line (PC3). The most potent compound exhibited good cytotoxic effects against the three cancer cell lines (IC50 values ranging from 12.09 to 26.49 μm) and induced cell-cycle retardation only on prostate cancer cells, which suggested that it might exert cell-type-specific effects.

Chloropicrin formation has been associated with ozonation followed by chlorination, but the reaction pathway and precursors have been poorly characterized. Experiments with methylamine demonstrated that ozonation converts methylamine to nitromethane at ∼100% yield. Subsequent chlorination converts nitromethane to chloropicrin at ∼50% yield under the conditions evaluated. Similarly high yields from other primary amines were limited to those with functional groups on the β-carbon (e.g., the carboxylic acid in glycine) that facilitate carbon-carbon bond cleavage to release nitromethyl anion. Secondary amines featuring these reactive primary amines as functional groups (e.g., secondary N-methylamines) formed chloropicrin at high yields, likely by facile dealkylation to release the primary nitro compound. Chloropicrin yields from tertiary amines were low. Natural water experiments, including derivatization to transform primary and secondary amines to less reactive carbamate functional groups, indicated that primary and secondary amines were the dominant chloropicrin precursors during ozonation/chlorination. Ozonation followed by chlorination of the primary amine side chain of lysine demonstrated low yields (∼0.2%) of chloropicrin, but high yields (∼17%) of dichloronitrolysine, a halonitroalkane structural analogue to chloropicrin. However, chloropicrin yields increased and dichloronitrolysine yields decreased in the absence of hydroxyl radical scavengers, suggesting that future research should characterize the potential occurrence of such halonitroalkane analogues relative to natural radical scavenger (e.g., carbonate) concentrations.

In this paper, heart-cutting two-dimensional GC/MS (GC-GC/MS) method in combination with a simple sample collection procedure was developed for the determination of 6 nitroalkanes in mainstream cigarette smoke. The method could remove large amounts of impurities on-line in the first polar column by heart-cuts and separate from the left interferences in a second mid-polar column. And the target compounds could be focused at the inlet of the second column by cryo-concentration. Compared to conventional GC/MS, GC-GC/MS achieved a lower noise level and sensitivity at least an order of magnitude higher. Furthermore, the GC-GC/MS method could avoid the false negative and false positive results that appeared in the compared conventional GC/MS analysis. By trapping the vapor phase of 20 cigarettes smoke, the LODs and LOQs of the nitroalkanes were 1.3 to 9.8 and 4.3 to 32.6ng/cigarette, respectively, and all linear correlation efficiencies were larger than 0.999. The validation results also indicate that the method has high accuracy (spiked recoveries between 84% and 102%) and good repeatability (RSD between 7.2% and 9.4%). The developed method was applied to analyze 1 Kentucky reference cigarette (3R4F) and 10 Chinese commercial brands of cigarettes. The research results indicated that nitromethane, nitroethane, 2-nitropropane and 1-nitro-n-pentane were detected in mainstream cigarette smoke, but 1-nitro-n-butane and 2-nitropropane, which were reported by one previous study, were not detected in all cigarette samples.

The promiscuity of de novo designed enzymes provides a privileged platform for diverse abiological reactions. In this work, we report the first example of a nitroolefin synthase that catalyzes the Henry condensation between aromatic aldehydes and nitromethane. Significant catalytic activity was discovered in the computationally designed and evolved carboligase RA95.5-8, and mutations around the active site were shown to improve the reaction rate, demonstrating the potential to optimize the enzyme by directed evolution. This novel nitroolefin synthase could participate in complex biological cascades, whereby the highly tunable chemoselectivity could afford useful synthetic building blocks.

Enzyme catalytic promiscuity is the ability of a single enzyme active site to catalyze several chemical transformations, among them those which are different from natural. We have attempted to use this feature of enzymes in the nucleophilic addition of nitromethane to aldimines (the aza-Henry reaction) whose chemically catalyzed version leads to synthetically useful β-nitroamines. We succeded in obtaining for the first time the desired products in the yields up to 81%. The most efficient proved lipase TL (from Pseudomonas stutzeri) and oxynitrilase from Arabidopsis thaliana. However, all the reactions investigated were non-stereoselective.

Sphingolipids have been considered for many years only as structural components of membranes. It is now acknowledged that they are also involved in controlling cellular processes such as proliferation.The present work was designed to find the anticancer activity of the crab Dromia dehanni hemolymph in in-vivo and in vitro with special reference to the anticancer compound sphingolipids isolation and characterization. The active fraction of the purified hemolymph was subjected to NMR and ESI-MS/MS analysis. The ESI-MS/MS spectrum exhibited intense signals for sodiated molecular ions [M + Na]+ of sphingomyelins (SM) identified as N-2-O-Acetyl-12 pentadecenoyl sphingosine phosphorylcholine, N-9-eicosenoyl- sphinganine phosphocholine and the corresponding dehydro sphingomyelin, N-9-eicosenoyl- dehydro- sphinganine phosphocholine along with the ions at m/z 147, 184 characteristic of phosphocholine. The present study revealed D. dehaani might be a great source for the novel anti-cancer compounds which can be used for human benefits.

Catalytic conditions for the α-arylation of aryl nitromethanes have been discovered using parallel microscale experimentation, despite two prior reports of the lack of reactivity of these aryl nitromethane precursors. The method efficiently provides a variety of substituted, isolable diaryl nitromethanes. In addition, it is possible to sequentially append two different aryl groups to nitromethane. Mild oxidation conditions were identified to afford the corresponding benzophenones via the Nef reaction, and reduction conditions were optimized to afford several diaryl methylamines.

In this work, a highly reproducible standard gas generating vial is proposed. The vial is comprised of a silicon diffusion pump oil spiked with an appropriate calibration compound, such as modified McReynolds probes (benzene, 2-pentanone, pyridine, 1-nitropropane, 1-pentanol, and n-octane), and then mixed with polystyrene/divinylbenzene (PS/DVB) particles. The concentrations of these compounds in gaseous headspace were found to substantially decrease in comparison to previously developed hydrocarbon pump oil based vials; hence, the amount of standard loaded onto SPME fibers was at most, half that of the previous vial design. Depletion for all compounds after 208 successive extractions was shown to be less than 3.5%. Smaller quantities of standards being used resulted in a vial that depleted slower while remaining statistically repeatable over a wider number of runs. Indeed, it was found that depletion could be largely predicted by using a mass balance theoretical model. This behavior allowed a further increase in the number of loadings that could be performed repeatedly. At a 95% level of confidence, the ANOVA test demonstrated that the prepared vials were statistically identical, with no significant intra- or inter-batch differences. In addition, it was found that vials stored under different conditions (e.g. under light exposure, room temperature, and within a refrigerator) were stable over 10 weeks. Silicon based vials proved to be ideal for performing instrument quality control and loading of internal standards onto fibers, both of which are of great importance when performing on-site analysis using portable GC-MS instrumentation and high throughput determinations in laboratory.

An efficient and mechanistically different method for the electrosynthesis of enaminone directly from methyl ketones, amines and nitromethane was developed. This transition-metal-free method proceeded at room temperature to give a wide array of enaminones in one step, utilizing nitromethane as the carbon source.

A novel one-pot strategy for the synthesis of 3-trifluoromethylquinoxalines from N-aryl enamines and nitromethane was developed. The tandem reaction is achieved through nitrosation of alkenes, tautomerization and cyclization, which can be applicable to a wide range of enamines with excellent functional group tolerance and afford quinoxalines in moderate to good yields.

Chemical syntheses generally involve a series of discrete transformations whereby a simple set of starting materials are progressively rendered more complex. In contrast, living systems accomplish their syntheses within complex chemical mixtures, wherein the self-organization of biomolecules allows them to form "assembly lines" that transform simple starting materials into more complex products. Here we demonstrate the functioning of an abiological chemical system whose simple parts self-organize into a complex system capable of directing the multistep transformation of the small molecules furan, dioxygen, and nitromethane into a more complex and information-rich product. The novel use of a self-assembling container molecule to catalytically transform a high-energy intermediate is central to the system's functioning.

Persulfate oxidation processes, with and without activation using ultraviolet light (respectively UV/PS and PS) have the potential to degrade anthropogenic chemicals in water. However, little is known about the impact of PS or UV/PS pre-oxidation on downstream formation of disinfection by-products (DBPs). In this study the three antibiotic chloramphenicols (chloramphenicol and two of its analogues [thiamphenicol and florfenicol], referred to collectively as CAPs), which frequently occur in wastewater-impacted source waters used by drinking water treatment plants, were selected as model antibiotic compounds. The formation of carbonaceous and nitrogenous disinfection by-products, including halomethanes, haloacetonitriles and halonitromethanes, during chlorination and chloramination preceded by PS and UV/PS was investigated. No significant concentrations of haloacetonitriles and halonitromethanes were detected during chlorination. During chloramination chloramphenicol formed a considerable amount of dichloronitromethane (e.g., 3.44 ± 0.33% mol/mol at NH2Cl dose = 1 mM) and trichloronitromethane (e.g., 0.79 ± 0.07% mol/mol at NH2Cl dose = 1 mM), compared with THM and HAN formation. PS pre-oxidation achieved a statistically significant reduction in trichloromethane formation from chlorination, and in HAN and HNM formation from chloramination. Although UV/PS slightly increased dichloroacetonitrile formation during chloramination, it significantly decreased dichloronitromethane and trichloronitromethane formation during chloramination. Overall, the use of PS and UV/PS has the potential to have contrasting impacts on DBP formation in heavily wastewater-impacted waters, depending on the disinfection method. Hence, their application needs to be carefully balanced against the downstream effect on DBP formation.

Enzymes are natural catalysts, controlling reactions with typically high stereospecificity and enantiospecificity in substrate selection and/or product formation. This makes them useful in the synthesis of industrially relevant compounds, particularly where highly enantiopure products are required. The flavoprotein pentaerythritol tetranitrate (PETN) reductase is a member of the Old Yellow Enzyme family, and catalyses the asymmetric reduction of β-alkyl-β-arylnitroalkenes. Under aerobic conditions, it additionally undergoes futile cycles of NAD(P)H reduction of flavin, followed by reoxidation by oxygen, which generates the reactive oxygen species (ROS) hydrogen peroxide and superoxide. Prior studies have shown that not all reactions catalysed by PETN reductase yield enantiopure products, such as the reduction of (E)-2-phenyl-1-nitroprop-1-ene (PNE) to produce (S)-2-phenyl-1-nitropropane (PNA) with variable enantiomeric excess (ee). Recent independent studies of (E)-PNE reduction by PETN reductase showed that the major product formed could be switched to (R)-PNA, depending on the reaction conditions. We investigated this phenomenon, and found that the presence of oxygen and ROS influenced the overall product enantiopurity. Anaerobic reactions produced consistently higher nitroalkane (S)-PNA product yields than aerobic reactions (64% versus 28%). The presence of oxygen dramatically increased the preference for (R)-PNA formation (up to 52% ee). Conversely, the presence of the ROS superoxide and hydrogen peroxide switched the preference to (S)-PNA product formation. Given that oxygen has no role in the natural catalytic cycle, these findings demonstrate a remarkable ability to manipulate product enantiopurity of this enzyme-catalysed reaction by simple manipulation of reaction conditions. Potential mechanisms of this unusual behaviour are discussed.

The Pd-catalyzed asymmetric allylic alkylation (AAA) reaction of nitromethane with monosubstituted allyl substrates was realized for the first time to provide corresponding products in high yields with excellent regio- and enantioselectivities. The protocol was applied to the enantioselective synthesis of (R)-baclofen and (R)-rolipram.

An efficient cross-coupling reaction of aryl halides and nitromethane was developed with the use of parallel microscale experimentation. The arylnitromethane products are precursors for numerous useful synthetic products. An efficient method for their direct conversion to the corresponding oximes and aldehydes in a one-pot operation has been discovered. The process exploits inexpensive nitromethane as a carbonyl equivalent, providing a mild and convenient formylation method that is compatible with many functional groups.

Building the building blocks: A highly enantioselective hydrogenation of β-aryl-β-alkyl disubstituted nitroalkenes 1 has been developed. This method results in enantiomerically pure nitroalkanes 2, which are versatile precursors for chemical synthesis.

A simple, environmentally friendly, and sustainable method for the synthesis of 3-nitro-2-arylimidazo[1,2-a]pyridine derivatives in moderate to good yields is presented.

An efficient asymmetric total synthesis of (S)-baclofen was accomplished via a one-pot operation from commercially available materials using sequential reactions, such as aldol condensation of acetaldehyde, diphenylprolinol silyl ether mediated asymmetric Michael reaction of nitromethane, Kraus–Pinnick oxidation, and Raney Ni reduction. Highly enantioenriched baclofen was obtained in one pot with a good yield over four reactions.

Organocatalytic asymmetric conjugate addition of α-nitroketones to β,γ-unsaturated α-keto esters has been developed. A pyrrolidine-based thiourea-tertiary amine was identified as the best catalyst. The reaction was found to proceed via cascade conjugate addition and acyl transfer reaction. A number of α-nitroketones and β,γ-unsaturated α-keto esters were examined in this transformation. 5-Nitro-2-acyloxypent-2-enoates were obtained in good yields (up to 99%) and enantioselectivities (up to 99% ee). The products could be hydrolyzed to provide 5-nitro-2-oxopentanoates, which are not available from the direct addition of nitromethane to β,γ-unsaturated α-keto esters.

The ReaxFF interatomic potential, used for organic materials, involves more than 600 adjustable parameters, the best-fit values of which must be determined for different materials. A new method of determining the set of best-fit parameters for specific molecules containing carbon, hydrogen, nitrogen and oxygen is presented, based on a parameter reduction technique followed by genetic algorithm (GA) minimization. This work has two novel features. The first is the use of a parameter reduction technique to determine which subset of parameters plays a significant role for the species of interest; this is necessary to reduce the optimization space to manageable levels. The second is the application of the GA technique to a complex potential (ReaxFF) with a very large number of adjustable parameters, which implies a large parameter space for optimization. In this work, GA has been used to optimize the parameter set to determine best-fit parameters that can reproduce molecular properties to within a given accuracy. As a test problem, the use of the algorithm has been demonstrated for nitromethane and its decomposition products.

Sodium methoxide-promoted methanolysis of 7-deoxy-7-nitro- l -glycero- l -galacto-heptitol peracetate rapidly and nearly quantitatively accumulates 7-deoxy-6-O-methyl-7-nitro- l -glycero- l -galacto-heptitol. The prolonged treatment then provides 76% of d -galactofuranosyl nitromethanes and finally results in the equilibrium of 77% of β- d -galactopyranosyl nitromethane and 7–9% of three other tautomeric d -galactosyl nitromethanes. Thermal treatment of 7-deoxy-7-nitro- l -glycero- l -galacto-heptitol in boiling water peaks at a 58% content of d -galactofuranosyl nitromethanes and ends in a similar equilibrium mixture of four d -galactosyl tautomers. The relevant kinetic parameters of the latter transformation are determined by a curve fitting using the nonlinear least-squares Marquardt–Levenberg algorithm.

Ruminal methanogenesis is considered a digestive inefficiency that results in the loss of 2-12% of the host's gross energy intake and contributes nearly 20% to the United States annual CH(4) emissions. Presently, the effects of the known CH(4) inhibitor, nitroethane, and two synthetic nitrocompounds, dimethyl-2-nitroglutarate and 2-nitro-methyl-propionate, on ruminal CH(4) production and fermentation were evaluated in vitro. After 24 h incubation at 39 degrees C under 100% CO(2), ruminal fluid cultures treated with 2.97 or 11.88 mumol ml(-1) of the respective nitrocompounds produced > 92% less CH(4) (P < 0.05) than non-treated controls. Quantification of fermentation end-products produced and H(2) balance estimates indicate that fermentation efficiencies were not compromised by the nitro-treatments.

A series of 1-substituted and 1,1-disubstituted taurines were synthesized from nitroolefins via the Michael addition with sodium ethylxanthate, oxidation with performic acid, and reduction with hydrogen in the presence of palladium on carbon powder. The current route is a versatile and salt-free method for synthesis of both aliphatic and aromatic 1-substituted and 1,1-disubstituted taurines.

The flavoenzyme nitroalkane oxidase catalyzes the oxidation of primary and secondary nitroalkanes to the corresponding aldehydes and ketones plus nitrite. The structure of the enzyme shows that Ser171 forms a hydrogen bond to the flavin N5, suggesting that it plays a role in catalysis. Cys397 and Tyr398 were previously identified by chemical modification as potential active site residues. To more directly probe the roles of these residues, the S171A, S171V, S171T, C397S, and Y398F enzymes have been characterized with nitroethane as substrate. The C397S and Y398 enzymes were less stable than the wild-type enzyme, and the C397S enzyme routinely contained a substoichiometric amount of FAD. Analysis of the steady-state kinetic parameters for the mutant enzymes, including deuterium isotope effects, establishes that all of the mutations result in decreases in the rate constants for removal of the substrate proton by approximately 5-fold and decreases in the rate constant for product release of approximately 2-fold. Only the S171V and S171T mutations alter the rate constant for flavin oxidation. These results establish that these residues are not involved in catalysis, but rather are required for maintaining the protein structure.

The flavoenzyme nitroalkane oxidase is a member of the acyl-CoA dehydrogenase superfamily. Nitroalkane oxidase catalyzes the oxidation of neutral nitroalkanes to nitrite and the corresponding aldehydes or ketones. Crystal structures to 2.2 A resolution or better of enzyme complexes with bound substrates and of a trapped substrate-flavin adduct are described. The D402N enzyme has no detectable activity with neutral nitroalkanes [Valley, M. P., and Fitzpatrick, P. F. (2003) J. Am. Chem. Soc. 125, 8738-8739]. The structure of the D402N enzyme crystallized in the presence of 1-nitrohexane or 1-nitrooctane shows the presence of the substrate in the binding site. The aliphatic chain of the substrate extends into a tunnel leading to the enzyme surface. The oxygens of the substrate nitro group interact both with amino acid residues and with the 2'-hydroxyl of the FAD. When nitroalkane oxidase oxidizes nitroalkanes in the presence of cyanide, an electrophilic flavin imine intermediate can be trapped [Valley, M. P., Tichy, S. E., and Fitzpatrick, P. F. (2005) J. Am. Chem. Soc. 127, 2062-2066]. The structure of the enzyme trapped with cyanide during oxidation of 1-nitrohexane shows the presence of the modified flavin. A continuous hydrogen bond network connects the nitrogen of the CN-hexyl-FAD through the FAD 2'-hydroxyl to a chain of water molecules extending to the protein surface. Together, our complementary approaches provide strong evidence that the flavin cofactor is in the appropriate oxidation state and correlates well with the putative intermediate state observed within each of the crystal structures. Consequently, these results provide important structural descriptions of several steps along the nitroalkane oxidase reaction cycle.

The catalytic asymmetric three-component 1,3-dipolar cycloaddition of 3-amino oxindoles with aldehydes and nitroolefins under the catalysis of a chiral phosphoric acid is reported. The reaction provides a facile approach to synthesize a diverse array of spiro[pyrrolidine-2,3′-oxindoles] in high yields with excellent diastereo- and enantioselectivities under mild conditions.

The combination of a catalytic amount of Cu(OTf)2 and less than a stoichiometric amount of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) under an O2 atmosphere effectively promoted the N-nitrosation of both secondary aromatic/aliphatic amines and tertiary aromatic amines with nitromethane (CH3NO2) leading to the preparation of N-nitrosamine derivatives.

A simple and mild Pd-catalysed carbonylative α-arylation of nitromethane has been realised providing access to α-nitro aryl ketones from an array of aryl and heteroaryl iodides. The methodology requires only a mild base and uses the convenient solid CO releasing molecule, COgen in a two-chamber system. Changing to the isotopically labelled (13)COgen, [(13)C]-acyl labelling can be effected through the generation of a near stoichiometric amount of (13)CO. Lastly, the significance of the generated products as synthetic intermediates is demonstrated.

Herein, we describe a short synthesis of 3-methyl-4-nitro-5-alkylethenyl isoxazoles and their reactivity as Michael acceptors. The title compounds reacted with nitromethane under phase-transfer catalysis to provide highly enantioenriched adducts (up to 93% ee) which were then converted to the corresponding γ-nitroacids.

In this manuscript we report a critical evaluation of the ability of natural DNA to mediate the nitroaldol (Henry) reaction at physiological temperature in pure water. Under these conditions, no background reaction took place (i.e., control experiment without DNA). Both heteroaromatic aldehydes (e.g., 2-pyridinecarboxaldehyde) and aromatic aldehydes bearing strong or moderate electron-withdrawing groups reacted satisfactorily with nitromethane obeying first order kinetics and affording the corresponding β-nitroalcohols in good yields within 24 h. In contrast, aliphatic aldehydes and aromatic aldehydes having electron-donating groups either did not react or were poorly converted. Moreover, we discovered that a number of metal-free organic buffers efficiently promote the Henry reaction when they were used as reaction media without adding external catalysts. This constitutes an important observation because the influence of organic buffers in chemical processes has been traditionally underestimated, Financial assistant by Universität Regensburg and SINCHEM Program (Erasmus Mundus Action 1 FPA 2013-0037) are gratefully acknowledged. D.D.D. thanks J.J. Marrero-Tellado for helpful discussions and DFG for the Heisenberg Professorship Award.

One approach to achieve fast and efficient separations in packed column liquid chromatography (LC) is to reduce eddy diffusion and mass transfer resistance in the mobile phase using short columns packed with small particles. In this study, efficiencies of columns packed with 1.5 and 3.0 microm nonporous and porous particles were compared in reversed-phase LC using nitromethane and a protein as analytes. Nonporous particles provided overall higher efficiency at high linear velocities when nitromethane was used as solute; however, the efficiency difference diminished significantly when the particle size was reduced from 3 to 1.5 microm. Efficiencies for 1.5 microm nonporous particles were considerably higher than those for 1.5 microm porous particles at high linear velocities when a protein, alpha-chymotrypsinogen A (MW 25,000), was used as solute. In addition, the average retention factor for amylbenzene in a column packed with ACQUITY C(18) porous particles was approximately 16 fold higher than for Micra C(18) nonporous particles for aqueous mobile phase compositions containing from 40 to 75% acetonitrile. Pressure drop, sample loading capacity, and separation power were also evaluated and compared for porous and nonporous particles under practical conditions.

Acid-catalysed methanolysis of 3,4,5,6-tetra- O -acetyl-1,2-dideoxy- l - arabino -hex-1-enitol proceeds via a cascade set of consecutive reactions resulting in its regiospecific conversion to a mixture of α- and β- C - l -arabinofuranosylmethanal dimethyl acetals and a mixed internal methyl acetal. Structures of the final products of the overall process provide unique evidence that a kinetically controlled, five-membered-ring closure precedes a six-membered-ring closure in reversible systems capable of giving both five-membered and six-membered all-sp 3 -atom rings. Determination of the reaction intermediate enabled extension of the Nef reaction to C -glycosylnitromethanes. Protonated aci -nitro forms of C -glycosylnitromethanes that are resistant to the Nef reaction in aqueous acidic media undergo a modified Nef reaction in acidified methanol, and the corresponding C -glycosylmethanal dimethyl acetals with α- l -arabinopyranosyl, β- d -glucopyranosyl, β- d -galactopyranosyl, β- d -mannopyranosyl and β- l -rhamnopyranosyl configurations were obtained in moderate yields.

The Henry reaction with the easily available alpha-d-xylo-pentodialdose afforded a diastereomeric mixture of nitroaldoses with the alpha-d-gluco- and beta-l-ido-configuration, respectively, in good yield. When n-BuLi was used as the base, the reaction afforded the alpha-d-gluco-nitroaldose as the only product. The reduction of the nitro group in the alpha-d-gluco- and beta-l-ido-nitroaldoses, removal of the protecting groups and intramolecular reductive cyclo-amination afforded the corresponding (2S,3R,4R,5R) and (2S,3R,4R,5S) tetrahydroxyazepanes.

A study of C-nucleophilic substitution at the C4-position on pyrimidine and C6-position on 2'-deoxyguanosine to produce novel nucleosides is presented with the spectroscopic properties of their respective substitution products. C4-(1,2,4-triazol-1-yl) pyrimidine nucleosides 1 were treated with nitroalkanes, malononitrile, acetylacetone, ethyl nitroacetate, acetoacetate and cyanoacetate at 100 degrees C in dioxane in the presence of DBU resulting in the production of novel nucleosides 2-11. To explore the application of this methodology to purine chemistry, this approach was used to produce novel analogs from 2'-deoxyguanosine. We found that the triazolo derivative 12 undergoes C-nucleophilic substitution with nitromethane, malononitrile, acetylacetone, ethyl nitroacetate and cyanoacetate in the presence of potassium carbonate (K2CO3) in DMF at 100 degrees C to give novel nucleosides 13-17.

A series of novel multifunctional amino alcohols were prepared by tandem Michael–Henry reaction by reacting nitroalkanes such as 2-nitropropane with readily available α,β-unsaturated aldehydes. The dinitro compounds were further reduced by catalytic hydrogenation to obtain respective diamines. This synthetic route provides a very convenient method of preparing multifunctional amino alcohols.

(2-Nitroethyl)benzene was identified as a major component of the flower scent of the Japanese loquat Eriobotrya japonica [Rosales: Rosaceae], together with p-methoxybenzaldehyde and methyl p-methoxybenzoate. The corresponding volatiles from chopped leaves did not contain these three compounds. This is the first time that 1-nitro-2-phenyl-ethane has been demonstrated to be a natural product among Japanese plants, although two Japanese millipedes are known to possess the same aromatics.

The peak capacity of small columns packed with 2.7 μm core–shell particles and 1.8 μm fully porous particles were compared at high temperatures using very steep (fast) gradient conditions and quite high linear velocities using the same instrument configuration as used to transfer first dimension effluent to the second dimension column as done in on-line comprehensive two-dimensional liquid chromatography. The experimental peak capacities of small columns (2.1 mm × 30 mm) packed with both types of particles were measured with fast gradients (9 s to 2 min) at high temperature (95 °C) using both the same flow rate (1.75 mL/min) and then at different flow rates at the same pressure (400 bar). Equal or slightly better peak capacities were achieved with the core–shell particle columns as compared to the fully porous particle columns at the same backpressure or the same flow rate. However, core–shell particles offer a real advantage over the smaller, fully porous particles because they can be operated at higher flow rates thus gradient mixer flush out and column reequilibration can be done in less time thereby allowing a greater fraction of the second dimension cycle time to be dedicated to the gradient time.

(−)-Horsfiline and (−)-coerulescine were synthesized through three one-pot operations in 33 and 46 % overall yield, respectively. Key to the success was the efficient use of a diarylprolinol silyl ether to catalyze the asymmetric Michael addition of nitromethane to a 2-oxoindoline-3-ylidene acetaldehyde. This allowed the all-carbon quaternary, spirocyclic carbon stereocenter to be constructed in good yield with excellent enantioselectivity.

The synthesis of (R,S)-[4-11C]baclofen, the first 11C-labeled GABAB agonist, was demonstrated via Michael addition of nitro[11C]methane as a key step. A tetrabutylammonium fluoride promoted Michael addition of nitro[11C]methane to methyl p-chlorocinnamate, followed by the nitro-group reduction in the presence of NiCl2 and NaBH4 in aqueous MeOH and alkaline hydrolysis yielded (R,S)-[4-11C]baclofen in 36.4 ± 1.8% radiochemical conversion in three steps within 20 min.

A chiral phosphine catalyzes the addition of a carbon nucleophile to the gamma position of an electron-poor allene (amide-, ester-, or phosphonate-substituted), in preference to isomerization to a 1,3-diene, in good ee and yield. This strategy provides an attractive method for the catalytic asymmetric gamma functionalization of carbonyl (and related) compounds.

The labelling synthesis of ethyl nitro[2-(11)C]acetate, a synthetic intermediate feasible for (11)C-labelled PET tracers, by C-carboxylation of [(11)C]MeNO(2) with 1-ethoxycarbonylbenzotriazole, and its simple application are presented.

The dichloro[(-)-sparteine-N,N']copper(II) complex provides Henry adducts with high enantioselectivities (73-97% ee) in Henry reaction between nitromethane and various aldehydes.

The reaction between pairs of enantiomeric cocrystals involving caffeine or theophylline and a chiral cocrystal former has been investigated by liquid-assisted grinding: we demonstrate two different outcomes for such cocrystal-cocrystal reactions.

Nucleoside analogues have played an important role in the viral decease and cancer therapy. To date, various nucleosides analogous have been investigated to improve their therapeutic effects and toxic properties. The modification of the sugar moiety has produced new active analogous. Especially, the design of furanose rings that include various heteroatoms has been one of the most useful approaches in the search for new nucleoside analogues with beneficial biological activity. Azanucleosides, in which the furanose oxygen atom is replaced by a nitrogen atom, have attracted interest because of possibility of their further modification through the nitrogen atom and structural similarity to the franose ring system. Considerable efforts have been dedicated to develop the efficient method for the synthesis of azanucleoside derivatives. Most of the synthetic strategies have been designed in order that N-glycosyl bond has been formed through an iminium ion intermediate. This process is necessary to incorporate a leaving group into the pyrrolidinyl precursor to generate the key reactive intermediate. However, access to such precursors requires a multi-step synthetic sequence, which includes cumbersome operations and harsh reaction condition. Indeed, this process often removes the opportunity of providing diverse azanucleosides based on further modification of the nitrogen atom. To address this challenge, we reasoned that direct and selective insertion of a nucleobase to the N-a position of prolinol moiety would avoid the redundant multi-step synthetic operation. We proposed that an electro-organic method might provide such an approach to overcome the challenge of direct introduction of a nucleobase into an unactivated pyrrolidine moiety. Previously, we have demonstrated the direct modification of pyrrolidine derivatives using LiClO4-CH3NO2 electrochemical oxidation system. This reaction system can accumulate desired iminium ion intermediates, anodically derived from N-protected pyrrolidine derivatives by C-H bound activation, enabling coupling with a variety of nucleophiles in one-pot reaction. In this conference, we report the electrochemical azanucleoside synthesis by coupling an unactivated prolinol derivative with a nucleobase through anodic oxidation using LiClO4-CH3NO2 solution system, and demonstrate the utility of this transformation by addition of various nucleophiles to readily available prolinol derivatives in a regioselective manner.

The high diastereoselectivity in the Michael addition of nitromethane to α,β-unsaturated γ-amino esters, crystal conformations of β-nitromethane substituted γ-amino acids and peptides are studied. Results suggest that the N-Boc protected amide NH, conformations of α,β-unsaturated γ-amino esters and alkyl side chains play a crucial role in dictating the high diastereoselectivity of nitromethane addition to E-vinylogous amino esters. Investigation of the crystal conformations of both α,β-unsaturated γ-amino esters and the Michael addition products suggests that an H-C(γ)-C(β)=C(α) eclipsed conformer of the unsaturated amino ester leads to the major (anti) product compared to that of an N-C(γ)-C(β)=C(α) eclipsed conformer. The major diastereomers were separated and subjected to the peptide synthesis. The single crystal analysis of the dipeptide containing β-nitromethane substituted γ-amino acids reveals a helical type of folded conformation with an isolated H-bond involving a nine-atom pseudocycle.